Zhang Lu, Chen Yubin, Yan Zhigang, Li Yuntai, Yang Xiaowen, Chen Li, Zhang Yanying, Chen Yingyu, Li Yonghui, Shi Qiumei, Wu Tonglei
Hebei Provincial Key Laboratory of Preventive Veterinary Medicine, Hebei Normal University of Science and Technology, Qinhuangdao, China.
Hebei Provincial Center for Livestock Breeding Improvement, Shijiazhuang, China.
Front Microbiol. 2025 Jun 24;16:1631008. doi: 10.3389/fmicb.2025.1631008. eCollection 2025.
Salmonellosis caused by sp. is a foodborne zoonotic disease that poses a significant threat to public health security. Vaccination is a safe and effective strategy for preventing and controlling infections. PipC is a chaperone protein associated with invasion proteins which is crucial for bacteria to invade host cells.
In this study, a Δ mutant strain was generated. Subsequently, we examined the environmental stress tolerance of the mutant strain through simulation experiments. Moreover, its virulence by employing cell and mouse infection models was investigated. Furthermore, we utilized a mouse model to further explore its potential as an attenuated live vaccine against serovar infection.
The strain C50336 with a deletion of the gene exhibits a significant reduction in its ability to resist environmental stress and virulence. Meanwhile, the expression levels of SPI-1-related genes (, , , , , and ) and SPI-2-related genes (, , , , , , , and ) encoding the type III secretion system (T3SS) were found to be decreased, leading to a significant reduction in the bacteria's invasion and intracellular survival abilities. The results of the mouse intraperitoneal challenge experiment showed that compared with the wild-type strain, the 50% lethal dose (LD) of the Δ strain increased by 47 times, and the bacterial loads in the liver, spleen, and cecum were significantly reduced. When mice were immunized with the Δ mutant strain, the immunized mice showed a robust immune response, with significantly increased cytokine and antibody levels in their bodies. Mice vaccinated with the Δ mutant strain had 100% immune protection against wild-type infection.
This study demonstrates that lack of affects pathogenicity by decreasing its virulence both and . Vaccination of mice with Δ conferred development of an acquired immunity and efficacious protection against experimental systemic infection. These results indicated that the Δ mutant strain can be used in the development of attenuated live vaccines.
由[沙门氏菌具体种名]引起的沙门氏菌病是一种食源性人畜共患病，对公共卫生安全构成重大威胁。疫苗接种是预防和控制[沙门氏菌具体种名]感染的安全有效策略。PipC是一种与侵袭蛋白相关的伴侣蛋白，对细菌侵入宿主细胞至关重要。
在本研究中，构建了一个Δ[缺失基因具体名称]突变株。随后，通过模拟实验检测了该突变株对环境应激的耐受性。此外，利用细胞和小鼠感染模型研究了其毒力。进一步地，我们使用小鼠模型进一步探索其作为抗[血清型具体名称]感染减毒活疫苗的潜力。
缺失[缺失基因具体名称]基因的C50336菌株抵抗环境应激的能力和毒力显著降低。同时，发现编码Ⅰ型Ⅲ型分泌系统（T3SS）的SPI-1相关基因（[具体基因名称1]、[具体基因名称2]、[具体基因名称3]、[具体基因名称4]、[具体基因名称5]和[具体基因名称6]）和SPI-2相关基因（[具体基因名称7]、[具体基因名称8]、[具体基因名称9]、[具体基因名称10]、[具体基因名称11]、[具体基因名称12]、[具体基因名称13]和[具体基因名称14]）的表达水平降低，导致细菌的侵袭和细胞内存活能力显著下降。小鼠腹腔注射攻毒实验结果表明，与野生型菌株相比，Δ[缺失基因具体名称]菌株的50%致死剂量（LD）增加了47倍，肝脏、脾脏和盲肠中的细菌载量显著降低。用Δ[缺失基因具体名称]突变株免疫小鼠时，免疫小鼠表现出强烈的免疫反应，体内细胞因子和抗体水平显著升高。用Δ[缺失基因具体名称]突变株接种的小鼠对野生型[沙门氏菌具体种名]感染具有100%的免疫保护作用。
本研究表明，[缺失基因具体名称]的缺失通过降低[沙门氏菌具体种名]的毒力，在体内和体外影响其致病性。用Δ[缺失基因具体名称]免疫小鼠可产生获得性免疫，并对实验性全身感染提供有效保护。这些结果表明，Δ[缺失基因具体名称]突变株可用于减毒活疫苗的开发。
